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Altered S100 Calcium-Binding Protein B and Matrix Metallopeptidase 9 as Biomarkers of Mesial Temporal Lobe Epilepsy with Hippocampus Sclerosis

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Abstract

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is the most common form of partial epilepsy. The aim of the present study is to highlight possible and suitable biomarkers that can help in the diagnosis and prognosis of this intractable form of epilepsy. The study was carried out on 30 epileptic patients of both sexes with complex partial seizures, having an age ranging from 4 to 30 years and were selected from the outpatient epilepsy clinic at the Kasr El-Aini Hospital in Cairo, Egypt. Thirty healthy children and young adults, age- and sex-matched to the patients, were included in the study as controls. Patients with epilepsy and healthy controls were subjected to a set of laboratory analyses including S100 calcium-binding protein B (S100B), matrix metallopeptidase 9 (MMP9), C-reactive protein (CRP), and prolactin (PRL), in addition to neurophysiological, radiological, and psychometric assessments, on the basis of the recent evidence of the field. The results of this study showed a marked increase in the investigated biomarkers in patients with epilepsy compared to controls. The performance of the epileptic patients in psychometric assessments was below the average threshold, with the MRI analysis showing specific findings of mesial temporal sclerosis (MTS) and EEG showing anterior temporal spikes. A significant negative correlation was found between MMP9 and psychometric test. On the other hand, a significant positive correlation was observed between seizure severity and the indicated biomarker. The present study suggests that S100B and MMP9 could be used as biomarkers for neuronal injury and helps in the prognosis of MTLE.

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References

  • Akanuma N, Alarco’n G, Lum F, Kissani N, Koutroumanidis M, Adachi N, Binnie CD, Polkey CE, Morris RG (2003) Lateralising value of neuropsychological protocols for presurgical assessment of temporal lobe epilepsy. Epilepsia 44:408–418

    Article  Google Scholar 

  • Alapirtti T, Waris M, Fallah M, Soilu-Hänninen M, Mäkinen R, Kharazmi E, Peltola J (2012) C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study. Epilepsia 53:790–796

    Article  CAS  Google Scholar 

  • Albeanu AG, Magureanu S, Lagae L (2012) The typical features of mesial temporal lobe epilepsy with hippocampal sclerosis in children. Rom J Neurol 11:127–134

    Google Scholar 

  • Allin KH, Nordestgaard BG, Flyger H, Bojesen SE (2011) Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study. Breast Cancer Res 13:R55. https://doi.org/10.1186/bcr2891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amruth G, Praveen-kumar S, Nataraju B, Kasturi P (2014) Study of psychiatric comorbidities in epilepsy by using the Mini International Neuropsychiatric Interview. Epilepsy Behav 33:94–100

    Article  CAS  Google Scholar 

  • Aravindkumar R, Shivashankar N, Satishchandra P, Sinha S, Saini J, Subbakrishna DK (2012) Temporal resolution deficits in patients with refractory complex partial seizures and mesial temporal sclerosis (MTS). Epilepsy Behav 24:126–130

    Article  Google Scholar 

  • Asadi-Pooya AA, Rostami C, Rabiei AH, Sperling MR (2015) Factors associated with tonic–clonic seizures in patients with drug-resistant mesial temporal epilepsy. J Neurol Sci 359:452–454

    Article  Google Scholar 

  • Bianchi R, Giambanco I, Donato R (2010) S100B/RAGE-dependent activation of microglia via NF-kappa B and AP-1 co-regulation of COX-2 expression by S100B, IL-1beta and TNF-alpha. Neurobiol Aging 31:665–677

    Article  CAS  Google Scholar 

  • Bone B, Fogarasi A, Schulz R, Gyimesi C, Kalmar Z, Kovacs N, Janszky J (2012) Secondarily generalized seizures in temporal lobe epilepsy. Epilepsia 53:817–824

    Article  Google Scholar 

  • Cersósimo R, Flesler S, Bartuluchi M, Soprano AM, Pomata H, Caraballo R (2011) Mesial temporal lobe epilepsy with hippocampal sclerosis: study of 42 children. Seizure 20:131–137

    Article  Google Scholar 

  • Cramer JA (2001) Exploration of changes in health-related quality of life after 3 months of vagus nerve stimulation. Epilepsy Behav 2(5):460–465

    Article  Google Scholar 

  • Diehl LA, Silveira PP, Leite MC, Crema LM, Portella AK, Billodre MN, Dalmaz C (2007) Long lasting sex-specific effects upon behavior and S100B levels after maternal separation and exposure to a model of post-traumatic stress disorder in rats. Brain Res 1144:107–116

    Article  CAS  Google Scholar 

  • Duncan JS, Sander JW (1991) The Chalfont seizure severity scale. J Neurol Neurosurg Psychiatry 54:873–876

    Article  CAS  Google Scholar 

  • El Missiry A (2003) Homicide and psychiatric illness: an Egyptian study. Dissertation, Ain Shams University, Cairo

  • First MB, Spitzer RL, Williams JB (1995) Structured clinical interview for DSM-IV (SCID-I): user’s guide and interview, research version. Biometrics, Research Department, New York State Psychiatric Institute, New York

    Google Scholar 

  • Fogarasi A, Arzimanoglou A (2011) The clinical syndrome of mesial temporal lobe epilepsy in children. In: Rosenow F, Ryvlin P, Lüders HO (eds) The mesial temporal lobe epilepsies. John Libbey Eurotext, Montrouge, pp 93–105

    Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the psychometric tests state of cases for the clinician. J Psychiatr Res 12:189–198

    Article  CAS  Google Scholar 

  • Fontana E, Negrini F, Francione S, Mai R, Osanni E, Menna E, Bernardina BD (2006) Temporal lobe epilepsy in children: electroclinical study of 77 cases. Epilepsia 47(Suppl 5):26–30

    Article  Google Scholar 

  • Galanopoulou AS, Moshé SL (2011) In search of epilepsy biomarkers in the immature brain: goals, challenges and strategies. Biomark Med 5:615–628

    Article  CAS  Google Scholar 

  • Getz K, Hermann B, Seidenberg M, Bell B, Dow C, Jones J, Woodard A (2003) Negative symptoms and psychosocial status in temporal lobe epilepsy. Epilepsy Res 53:240–244

    Article  Google Scholar 

  • Ghanem MH, Ibrahim M, El-Behairy AA, El Merghany H (2000) Mini international neuropsychiatric interview for children/adolescents (M.I.N.I. Kid), Arabic version, 1st edn. Institute of Psychiatry, Ain Shams University, Cairo

    Google Scholar 

  • Gomez-Ibañez A, Gasca-Salas C, Urrestarazu E, Viteri C (2013) Clinical phenotypes within non-surgical patients with mesial temporal lobe epilepsy caused by hippocampal sclerosis based on response to antiepileptic drugs. Seizure 22:20–23

    Article  Google Scholar 

  • Heuser K, Cvancarova M, Gjerstad L, Tauboll E (2011) Is temporal lobe epilepsy with childhood febrile seizures a distinctive entity? A comparative study. Seizure 20:163–166

    Article  Google Scholar 

  • Javidan M (2012) Electroencephalography in mesial temporal lobe epilepsy: a review. Epilepsy Res Treat 2012:637430. https://doi.org/10.1155/2012/637430

    Article  PubMed  PubMed Central  Google Scholar 

  • Kar BR, Rao SL, Chandramouli BA, Thennarasu K, Satishchandra P (2010) Neuropsychological lateralization of brain dysfunction in children with mesial temporal sclerosis: a presurgical evaluation. J Child Neurol 25:705–714

    Article  Google Scholar 

  • Kim WJ, Park SC, Lee SJ, Lee JH, Kim JY, Lee BI, Kim DI (1999) The prognosis for control of seizures with medications in cases with MRI evidence for mesial temporal sclerosis. Epilepsia 40:290–293

    Article  CAS  Google Scholar 

  • Konopka A, Grajkowska W, Ziemiańska K, Roszkowski M, Daszkiewicz P, Rysz A, Marchel A, Koperski L, Wilczyński GM, Dzwonek J (2013) Matrix metalloproteinase-9 (MMP-9) in human intractable epilepsy caused by focal cortical dysplasia. Epilepsy Res 104:45–58

    Article  CAS  Google Scholar 

  • Kumlien E, Doss RC, Gates JR (2002) Treatment outcome in cases with mesial temporal sclerosis. Seizure 11:413–417

    Article  Google Scholar 

  • Lu C, Li J, Sun W, Feng L, Li L, Liu A, Wang Y (2010) Elevated plasma S100B concentration is associated with mesial temporal lobe epilepsy in Han Chinese: a case-control study. Neurosci Lett 484:139–142

    Article  CAS  Google Scholar 

  • Luef G (2010) Hormonal alterations following seizures. Epilepsy Behav 19:131–133

    Article  Google Scholar 

  • Macizo P, Soriano MF, Paredes N (2016) Phonological and visuospatial working memory in autism spectrum disorders. J Autism Dev Disord 46(9):2956–2967

    Article  CAS  Google Scholar 

  • Mikkonen K, Pekkala N, Pokka T, Romner B, Uhari M, Rantala H (2012) S100B proteins in febrile seizures. Seizure 21:144–146

    Article  Google Scholar 

  • Miró J, Gurtubay-Antolin A, Ripollés P, Sierpowska J, Juncadella M, Fuentemilla L, Sánchez V, Falip M, Rodríguez-Fornells A (2015) Interhemispheric microstructural connectivity in bitemporal lobe epilepsy with hippocampal sclerosis. Cortex 67:106–121

    Article  Google Scholar 

  • Okulski P, Jay TM, Jaworski J, Duniec K, Dzwonek J, Konopacki FA, Kaczmarek L (2007) TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the prefrontal cortex. Biol Psychiatry 62:359–362

    Article  CAS  Google Scholar 

  • Ouvrier RA, Goldsmith RF, Ouvrier S, Williams IC (2016) The Value of the Mini-Mental State Examination in Childhood: A Preliminary Study. J Child Neurol 8(2):145–148

    Article  Google Scholar 

  • Pittau F, Bisulli F, Mai R, Fares JE, Vignatelli L, Labate A, Tinuper P (2009) Prognostic factors in cases with mesial temporal lobe epilepsy. Epilepsia 50:41–44

    Article  Google Scholar 

  • Romi F, Helgeland G, Gilhus NE (2012) Serum levels of matrix metalloproteinases: implications in clinical neurology. Eur Neurol 67:121–128

    Article  CAS  Google Scholar 

  • Rudie JD, Colby JB, Salamon N (2015) Machine learning classification of mesial temporal sclerosis in epilepsy patients. Epilepsy Res 117:63–69

    Article  Google Scholar 

  • Schilbach L, Koubeissi MZ, David N, Vogeley K, Ritzl EK (2007) Being with virtual others: studying social cognition in temporal lobe epilepsy. Epilepsy Behav 11:316–323

    Article  Google Scholar 

  • Selwa LM, Schmidt SL, Malow BA, Beydoun A (2003) Long-term outcome of nonsurgical candidates with medically refractory localization-related epilepsy. Epilepsia 44:1568–1572

    Article  Google Scholar 

  • Sendrowski K, Sobaniec W (2013) Hippocampus, hippocampal sclerosis and epilepsy. Pharmacol Rep 65:555–565

    Article  CAS  Google Scholar 

  • Sendrowski K, Sobaniec W, Sobaniec-Lotowska ME, Lewczuk P (2004) S-100 protein as marker of the blood-brain barrier disruption in children with internal hydrocephalus and epilepsy--a preliminary study.  Rocz Akad Med Bialymst 49:236–238

    PubMed  Google Scholar 

  • Shapiro LA, Bialowas-McGoey LA, Whitaker-Azmitia PM (2010) Effects of S100B on serotonergic plasticity and neuroinflammation in the hippocampus in down syndrome and Alzheimer’s disease: studies in an S100B overexpressing mouse model. Cardiovasc Psychiatry Neurol 2010:153657. https://doi.org/10.1155/2010/153657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheehan DV, Janavs J (1998) Mini international neuropsychiatric interview for children/adolescents (M.I.N.I. Kid). University of South Florida College of Medicine, Tampa

    Google Scholar 

  • Silvia O, Patricia S, Damián C, Brenda G, Walter S, Luciana D, Estela C, Patricia S, Silvia K (2003) Mesial temporal lobe epilepsy and hippocampal sclerosis: cognitive function assessment in Hispanic patients. Epilepsy Behav 4:717–722

    Article  Google Scholar 

  • Siniscalchi A, Gallelli L, Mercuri NB, De Sarro G (2008) Serum prolactin levels in repetitive temporal epileptic seizures. Eur Rev Med Pharmacol Sci 12:365–368

    CAS  PubMed  Google Scholar 

  • Suenaga N, Ichiyama T, Kubota M, Isumi H, Tohyama J, Furukawa S (2008) Roles of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in acute encephalopathy following prolonged febrile seizures. J Neurol Sci 15:126–130

    Article  Google Scholar 

  • Sutula TP (2004) Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development. Epilepsy Res 60:161–171

    Article  Google Scholar 

  • Wechsler D (1996) Wechsler Intelligence Scale for Children-Third Edition. WISC-III. Psychological Corporation, San Antonio 

    Google Scholar 

  • Wechsler D (1997) WAIS-III: Wechsler adult intelligence scale. Psychological Corporation, San Antonio

    Google Scholar 

  • Wechsler D (2004) The Wechsler intelligence scale for children, 4th edn. Pearson, London

    Google Scholar 

  • Westaby S, Saatvedt K, White S, Katsumata T, van Oeveren W, Bhatnagar NK, Brown S, Halligan PW (2000) Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass? J Thorac Cardiovasc Surg 119:132–137

    Article  CAS  Google Scholar 

  • Wilczynski GM, Konopacki FA, Wilczek E, Lasiecka Z, Gorlewicz A, Michaluk P, Wawrzyniak M, Malinowska M, Okulski P, Kolodziej LR, Konopka W, Duniec K, Mioduszewska B, Nikolaev E, Walczak A, Owczarek D, Gorecki DC, Zuschratter W, Ottersen OP, Kaczmarek L (2008) Important role of matrix metalloproteinase 9 in epileptogenesis. J Cell Biol 180:1021–1135

    Article  CAS  Google Scholar 

  • Winocur G, Roder J, Lobaugh N (2001) Learning and memory in S100-beta transgenic mice: an analysis of impaired and preserved function. Neurobiol Learn Mem 75:230–243

    Article  CAS  Google Scholar 

  • Yin P, Yang L, Zhou HY, Sun RP (2011) Matrix metalloproteinase-9 may be a potential therapeutic target in epilepsy. Med Hypotheses 76:184–186

    Article  CAS  Google Scholar 

  • Zinke K, Fries E, Altgassen M, Kirschbaum C, Dettenborn L, Kliegel M (2010) Visuospatial short-term memory explains deficits in tower task planning in high-functioning children with autism spectrum disorder. Child Neuropsychol 16(3):229–241

    Article  Google Scholar 

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Correspondence to Geir Bjørklund.

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All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Meguid, N.A., Samir, H., Bjørklund, G. et al. Altered S100 Calcium-Binding Protein B and Matrix Metallopeptidase 9 as Biomarkers of Mesial Temporal Lobe Epilepsy with Hippocampus Sclerosis. J Mol Neurosci 66, 482–491 (2018). https://doi.org/10.1007/s12031-018-1164-5

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